Characteristics of Kidney Resident IgA Antibody-Secreting Cells in IgA Nephropathy
Bibliographic record
Abstract
Background: The trigger and sources of pathogenic IgA in IgAN are not established. Prevailing theories suggest that circulating polymeric nephritogenic IgA is produced by either antibody secreting cells located within the mucosa-associated lymphoid tissue or the bone marrow. Our recent work demonstrated that in experimental IgAN mice (BAFF-Tg), mucosal pathobiont-directed IgA antibody secreting cells (APC) are identified within the kidney. In the current study we aimed to characterize kidney IgA APC in experimental IgAN, and to elucidate the factors that foster migration to and residence within the kidney and explore cell-cell interactions within the kidney niche. Methods: Flow cytometry was used to identify IgA APC in the kidneys of the male BAFF-Tg and C57/BL6 (WT). Single-cell mRNA sequencing (scRNA-seq) was performed in 4 BAFF-Tg and 4 WT at 20 weeks of age to characterize immune cells within the kidney. Results: We identified an age-dependent increase in IgA-producing plasma cells (PC) by flow cytometry (CD45+, B220-, CD98+, IRF4+, IgA+) within the kidneys of BAFF-Tg but not WT mice; these PC were detectable at 6 weeks of age, and numbers continued to rise by 20 weeks of age. scRNA-seq confirmed a population of IgA APC in the BAFF-Tg kidneys. Analysis of differential gene expression supported phenotypically different subpopulations of IgA APC in kidneys of BAFF-Tg. Ligand-receptor pair analysis suggests cell-cell interaction patterns between IgA APC, macrophages and endothelial cells that may support migration of IgA APC and proliferation of these cells within the kidney. Conclusions: Our mouse data support the concept that pathogenic IgA production in experimental IgAN can occur within the kidney. We have confirmed the age-dependent presence of IgA-producing PC within the kidneys of the BAFF-Tg by flow cytometry and these cells may be initially proliferating within the kidney. We have further characterized the immune cell populations within the kidney in experimental IgAN using scRNA-seq, and identified possible cell-cell interactions that may foster the migration and support of mucosal derived IgA APC within the kidney, potentially resulting in kidney pathology. Elucidation of the ligands and receptors involved in kidney IgA APC migration and residence will inform therapeutic interventions for the treatment of IgAN.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".